Microbial Cellulose Wound Dressing in the Treatment of Nonhealing Lower Extremity Ulcers

Abstract: Following standard care, nonhealing lower extremity (LE) ulcers were managed with a bacterial cellulose (BC) wound dressing, Dermafill™, (AMD/Ritmed, Tonawanda, NY), derived from Acetobacter xylinum. The time to 75% reduction in wound size was compared in 11 chronic wounds before and after the application of BC. The mean period of observation before the application of BC was 315 days; (95% CI: 239–392 days). With the application of BC to these chronic wounds, the mean time to 75% epithelization was reduced to 81 days (95% CI: 50–111 days) with a median of 79 days. The rate of wound closure with BC was significantly faster than with standard care (P < 0.001). When applied to nonhealing LE ulcers, a BC wound dressing shortens the time to wound closure over standard care.

Address correspondence to: Dennis J. Levinson, MD Department of Medicine Michael Reese Hospital 2929 S. Ellis Ave. Chicago, IL 60616 Phone: 312-791-2670 E-mail: djlevins@uic.edu
Disclosure: Dr. Levinson discloses stock ownership in MCT Woundcare, LLC, a distributor of microbial cellulose.
     Tissue viability, infection, moisture imbalance, and nonadvancing or undermined margins, are factors that may impede the wound healing process resulting in chronic nonhealing wounds.¹ Among the many factors involved in the management of the chronic wound, perhaps one of the most important is the wound dressing.² This retrospective, observational study reports initial results on the use of a transparent, semipermeable, occlusive, bacterial cellulose (BC) dressing derived from Acetobacter xylinum in nonhealing ulcers of the lower extremity (LE).

Materials and Methods

     The primary outcome was a sequential paired comparison of the rate of reduction in wound area during treatment with either standard dressings or BC. Only wounds that failed to heal following 60 or more days of treatment with standard dressings were selected for application of BC. Time to 75% epithelization was selected as the endpoint, since this provided an equivalent endpoint that could be compared for the same wound treated with standard and BC dressings. The study population was derived from a retrospective chart review of patients who received treatment in the outpatient wound care clinic at Michael Reese Hospital (Chicago, IL). Patients were excluded if they had evidence of infections such as osteomyelitis, cellulitis, cancer, or renal failure. Standard care included either enzymatic, mechanical or sharp debridement (as needed), 2- or 4-layer bandages for venous hypertension, and off-loading for diabetic ulcers. Wound dressings employed in standard treatment of chronic wounds before the application of BC included gauze, foams and alginates, composites, and silver impregnated polymers. The protocol was approved by the hospital’s independent review board.

Statistical Analysis

     The outcome measurement was the rate of relative reduction in wound area. A baseline measurement at the first clinic visit was used for calculation of the change in wound area. In nonhealing wounds where BC was applied to wounds previously treated with standard dressings, the baseline area of the wound was reset to the area at the time of initial BC application. Kaplan-Meier analysis was applied to estimate the time to the outcome event—the time to the first clinic visit where the percent area epithelized was greater than 75%.

Results

     In chronic LE ulcers that failed to heal using standard dressings, BC was applied to the same wounds, and the time to 75% reduction in wound size was compared to wound size and duration prior to BC application. Eleven patients were evaluated, 6 (55%) of whom were women. The average age was 70 years with a range of 51 to 87 years. Six patients had diabetes and 5 had a post-phlebitic syndrome.      Prior to the application of BC, only 3 of 11 wounds reached 75% closure with a mean healing time of 315 days (95% CI; 239–392 days: Figure 1). The mean area of the wounds before the application of BC was 53 cm² ± 16.8. Subsequent treatment of nonhealing ulcers with BC resulted in 7 of 11 wounds reaching 75% improvement within 81 days (95% CI; 50–111 days). The difference in the rate of epithelization between BC and standard care was statistically significant (P < 0.001; Cox Regression, Figure 1). Application of BC in a 54-year-old with diabetes is shown in Figure 2.

Discussion

     Bacterial cellulose is a biosynthetic microfibrillar cellulose membrane produced from the nonpathogenic organism, Acetobacter xylinum. The extracellular cellulose is identical to plant cellulose. Extracellular cellulose however, is free of lignin, pectin, and hemicellulose. This microfibrillar cellulose membrane also has greater crystallinity, water absorption capacity, and mechanical strength in the wet state.³ As a temporary skin substitute used in partial-thickness burns, graft sites, pressure ulcers, and other acute and chronic wounds, observations of BC include immediate pain relief, reduced infection rate, membrane transparency, and faster healing. The BC also has autolytic debridement properties, biodegrades following epithelization, and reduces treatment time and costs.^4–7      In 2004, Alvarez et al⁸ demonstrated improved time to granulation tissue formation and epithelization in chronic venous ulcers treated with BC when compared to a standard treatment with petrolatum impregnated gauze. The authors suggest that BC creates a protective moist environment similar to a blister roof, thereby improving debridement and epidermal resurfacing while reducing pain.

Conclusion

     In this preliminary study, a BC wound dressing was used to assist in the management of chronic lower extremity ulcers. The primary outcome, 75% surface epithelization, was significantly improved in chronic wounds of diverse etiology, an observation also made by Alvarez et al⁸ in chronic venous ulcers. The authors agree with Alvarez et al that the BC forms a semipermeable occlusive barrier that can enhance macrophage activity, fibrinolysis, and angiogenesis.